This project is focused on the genetics of hereditary hearing impairment. The DFNB7 locus is found in several families from India. Two families have a cumulative LOD score of 9. The region of linkage is refined to a 4 cM interval on chromosome 9p12-q13. This region of linkage is syntenic to the deafness mouse locus on mouse chromosome l9. Recently, a family from the United States has started to participate in the study of DFNB7. This U.S. family has an autosomal dominant progressive hearing loss and an inversion at 9p11-q13. It is hypothesized that the inversion is disrupting the DFNB7 locus and can be used as a marker in cloning this gene. Work is in progress to better define the inversion break points and also to clone the DFNB7 locus. Multiple alleles of the DFNB3 locus have been found in a large family from Newfoundland. This same family is also linked to several loci, suggesting that the heterogeneous population of Canada and the United States has many mutations in loci responsible for nonsyndromic hearing impairment, and that these mutant loci are present in a high enough proportion of the population to cause hearing impairment when nonconsanguineous people marry and have children. Two consanguineous families from India are linked to the DFNB3 locus. A LOD score of 4 has been reached for one family with 4 affected out of 9 children. A LOD is yet to be computed for a family with 5 affected children out of 6 total children. It is presumed that this family will also support a LOD above 3, as per simulations using SLINK, a computer program used in simulating linkage LOD scores.